Protein separation and purification using inorganic oxide materials: from surface chemistry to biochemical applications

Inorganic oxide materials are widely used for protein and peptide separation because their surfaces support multiple types of interactions, including metal-centered coordination, electrostatic interactions, and both hydrophilic and hydrophobic interactions. This review summarizes the binding mechanisms between proteins/peptides and representative inorganic oxides – ZrO2, TiO2, SiO2, Fe3O4, Al2O3, ZnO, CeO2, SnO2, Nb2O5, Ta2O5, and Ga2O3. Particular emphasis is placed on the comparative analysis of adsorption mechanisms across these inorganic oxides and on factors such as crystal structure, surface acidity, and surface functionalization that influence adsorption selectivity. The review further discusses the effects of surface chemistry on purification performance and their combined effects on multi-step purification workflows. Recent advances in surface engineering and hybrid material design are highlighted to provide perspectives for the development of selective and mild protein purification processes. This framework offers guidance for the rational selection of inorganic oxide materials, enabling reproducible, selective, and mild purification of diverse proteins and peptides in biopharmaceutical applications.